Although glucocorticoids, such as prednisone, have been employed for decades for control of hearing loss, little is known of the cellular mechanisms of the ear that are under their control. A better understanding of these steroid responsive mechanisms is criticai for our design of appropriate therapy. Therefore, the long term goal of this research is to characterize the steroid driven cellular mechanisms of the ear. Preliminary studies have shown hearing loss in the MRL/MpJ-Fas(lpr) autoimmune mouse responds to treatment with both the glucocorticoid prednisolone and the mineralocorticoid aldosterone. It is hypothesized that two steroid responsive mechanisms exist in the ear: a direct sodium transport effect in the stria vascularis mediated by the mineralocorticoid receptor, and an indirect systemic immune suppression mechanism mediated by the glucocorticoid receptor. The planned studies will characterize these steroid driven processes with steroid treatments that will selectively isolate and measure the cellular and molecular events they control. The specific aims to investigate these steroid mechanisms of the ear are:Aim 1: Establish the lowest effective dose of the mineralocorticoid and glucocorticoid for control of inner ear function and systemic autoimmune disease.Aim 2: Determine the lowest combination dose of the two steroids that can effectively control the inner ear dysfunction and systemic autoimmune disease.Aim 3: Determine which steroid receptor is mediating steroid control of cochlear function.Aim 4: Determine if the middle ear route of steroid delivery is a feasible treatment for either steroid control of autoimmune hearing loss.In all studies, assessment will be made of steroid effects on inner ear structure (light and electron microscopy), function (ABR, EP), cochlear specific antibodies (ELISA), and upregulated gene products (ELISA). The results from these studies will provide significant new findings regarding the cellular and molecular mechanisms of the ear that are under the control of steroids. This study also will lay important groundwork for the development of alternative steroid therapies that may be more effective than those currently employed for clinical hearing loss.